rs758706191
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_033453.4(ITPA):c.488C>T(p.Thr163Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000616 in 1,461,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T163T) has been classified as Likely benign.
Frequency
Consequence
NM_033453.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPA | NM_033453.4 | c.488C>T | p.Thr163Met | missense_variant, splice_region_variant | 7/8 | ENST00000380113.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPA | ENST00000380113.8 | c.488C>T | p.Thr163Met | missense_variant, splice_region_variant | 7/8 | 1 | NM_033453.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250934Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135702
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461266Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726960
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 35 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | TIDEX, University of British Columbia | - | - - |
Inosine triphosphatase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 163 of the ITPA protein (p.Thr163Met). This variant is present in population databases (rs758706191, gnomAD 0.006%). This missense change has been observed in individual(s) with ITPase deficiency (PMID: 30542205, 35098521). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 431714). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at